Ebola and Marburg viruses, the only members of the family Filoviridae, cause hemorrhagic fevers which are lethal in up to 90% of human cases. No vaccine or antiviral therapy currently exists to prevent or treat Filovirus infection. Due to their exceptional lethality and potential for weaponization, these viruses have been identified as key biodefense targets in both Project Bioshield and the NIAID Biodefense Research agenda. Hawaii Biotech, Inc. has successfully produced several recombinant Ebola virus proteins which show strong immunogenicity and protective efficacy in mice. The specific goals of this project are to expand the antigenic repertoire of the vaccine candidate to induce broad protection against both Ebola and Marburg viruses, to confirm the protective efficacy of the vaccine formulations in guinea pig and non-human primate models, and to ready the product for preclinical development in Phase II. The challenge studies will represent the preclinical proof of concept for the approach, while the inclusion of additional glycoproteins will ensure that the vaccine candidate induces broad protective immunity against the most pathogenic Filovirus strains. The vaccine candidate has potential as a stand alone or as a partner in a prime-boost approach in combination with other vaccine candidates currently being developed by the NIAID Vaccine Research Center. A safe and efficacious vaccine utilizing recombinant subunit proteins would fill an important need in the country's biodefense preparedness strategy. [unreadable] [unreadable] [unreadable]